Colours in Pharmaceutical Products

Transcription

1 Colour Management For Formulators 23 rd October 2013 Colours in Pharmaceutical Products Marcel Cimpan Senior Manager Customer and Technical Services

2 Agenda Uses for colours in the Pharmaceutical industry Colorcon Brand Enhancement Services Pigments available Oxides Lakes Non synthetics Global colours Regulatory Quantity restrictions Film coat formulation Colour measurement and control Coating application

3 Uses for colours Colouring of coating systems Colouring of core tablets Colouring of liquid and semi-solid products Food and confectionery

4 Why differentiate at the dosage level? Do you recognize this drug? No trademark protection No brand equity Increased risk of mix up on the production line and therefore potential product recall Increased risk of counterfeiting No distinctive shape and color No memorable image Lack of branding does not help patient compliance

5 Disturbing Facts. Medication errors cause (FDA) At least are sickened, injured or killed each year (Washington Post) Treating the related injuries ( Washington Post)

6 FDA Concern! " # # #

7 FDA Draft Guidance Different strengths same look - $

8 There is a need to differentiate Patients are consumers Studies have proven that consumers form an emotional link with colour* Examples of drugs where GERX manufacturer used unique shape/color and got higher counting unit sales than others are in the following slides * (ref: Some aesthetic considerations for over-the-counter (OTC) pharmaceutical products; International Journal of Biotechnology, Volume 11, 2010)

9 Branded Generics with higher market shares than plain, white tablets Therapy Generic name/api Tablet image Manufacturer Coated or uncoated 2012 CU (000 s) Quetiapine 25mg Teva Coated 145,656 Quetiapine 25mg Lupin Coated 119,586 Antipsychotic Quetiapine 25mg Roxane Uncoated 73,676 * tablets are not to scale so size comparisons should not be made

10 Branded Generics with higher market shares than plain, white tablets Therapy Generic name/api Tablet image Manufacturer Coated or uncoated 2010 CU (000 s) 2011 CU (000 s) 2012 CU (000 s) Levetiracetam 750 mg Lupin Coated 133, , ,142 Anticonvulsant Levetiracetam 750 mg Mylan Coated, white 195, , ,016 Interestingly Mylan was the first to file, but after the first year volume dropped to the pigmented Lupin dose * tablets are not to scale so size comparisons should not be made

11 Brand Enhancement Services Colorcon can help you differentiate: Therapeutic Category Color Preference Tablet Design Session Mechanical Drawings Tablet Prototypes Powerful Stage 1 Stage 2 Stage 3 Stage 4 Stage 5 Improving speed to market from months to weeks

12 Pigments used in film coatings Metal Oxides Titanium Dioxide Iron Oxide Red Iron Oxide Yellow Iron Oxide Black Aluminium Lakes Non synthetics

13 Types of Pigment Oxides - Titanium and Iron good chemical and light stability small particle size little batch-to-batch colour variation low cost Advantages excellent opacity wide regulatory acceptability restricted colour range rather dull colours Disadvantages

14 Types of Pigment Aluminium lakes wide range of bright colours brightness retained when mixed together Advantages low opacity compared with other pigments colour depends on particle properties - batch variation tendency to form gel structure in liquid products Disadvantages some colours show poor stability

15 Types of Pigment Non-synthetic colours natural or nature-identical claim consumer acceptability? Advantages low colour strength high cost residual taste and odour restricted colour range Disadvantages batch-to-batch color variation very poor chemical and light stability

16 Examples of non synthetic colours Examples of colours exempted from certification Examples of colours approved for ingested drugs Annatto extract Dehydrated beets (beet powder) Caramel [beta]-apo-8'-carotenal [beta]-carotene Cochineal extract; carmine Toasted partially defatted cooked cottonseed flour Grape color extract Paprika Paprika oleoresin Mica-based pearlescent pigments Riboflavin Saffron Tomato lycopene extract; tomato lycopene concentrate Turmeric Turmeric oleoresin

17 Global Acceptable Pharma Colors US, EU, Japan Only a limited number of colors are acceptable for global (US/EU/JP) use: FD&C Blue # 2 (Indigo Carmine) FD&C Blue # 1 (Brilliant Blue) FD&C Yellow # 6 (Sunset Yellow) Titanium Dioxide Iron Oxide Red Iron Oxide Yellow Iron Oxide Black

18 Regulatory restrictions - summary - Country specific - Main regulatory bodies: FDA (USP, GRAS), EU, JP - All these will list colorants exempted from certification, approved colorants, approved colourants with quantitative limits, banned colouring agents - In some cases there will be specific regulations or labelling requirements when used in products for children (age specific, eg EU under 36 month) - Specific labelling requirements when used in food additives or nutritional products - Indigo carmine - JP max 0.1% by w. of color - BOx - JP max mg/day oral USP 5mg/day elemental iron - ROx - JP max 95.4 mg/day oral USP 5mg/day elemental iron - YOx - JP max 5.67 mg/day oral USP 5mg/day elemental iron - Sunset yellow - JP max 0.1% by w. of color Example: Japanese regulatory only allows 5.67mg of yellow iron oxide per day. For a 1000mg tablet a 3% weight gain of film is 30mg: - one tablet a day could therefore contain a maximum of 5.67mg YOx - four tablets a day is mg YOx

19 Coating formulation Opadry Complete Film Coating System A pre-dispersed powder containing. Polymer Plasticizer Pigment. in optimal ratios

20 Colour measurement CIELab Measurement Factors influencing colour

21 Representation of CIEL*A*B* Colour Space Colour space diagram courtesy of Datacolor

22 CIEL*A*B* - Colour Space Diagram L Light (100 = White) Blue -b +a Red Standard expressed in terms of L, a, b values, e.g. L = 55 a = +14 b = +10 Green -a L +b Yellow Acceptable colour limit defined as a sphere around the standard point Dark (0 = Black)

23 Colour Control - Reflectance Spectrophotometry Standard white drawdown card Liquid dispersion of sample Drawdown using standard thickness bar Measure quantity of light reflected across the visible spectrum

24 Colour Control - Reflectance Spectrophotometry % light reflected Standard Production Batch , nm Blue Red

25 Factors Influencing Colour Type of light used (metamerism) Colour is subjective: COLOUR IS A SENSATION WHICH ONLY EXISTS INSIDE THE BRAIN Tablet shape Tablet coating roughness

26 Coating application

27 Coating application spray gun Manesty ABC

28 Coating application

29 Coating application coating system comparison Evaluation of Tablets Color development and uniformity Sampled at 5 minute intervals and compared to the final tablet reference color Target 1 DE from reference DE = DE = 0.59

30 Coating application coating system comparison Final Tablet Appearance Opadry II PVA HPMC

31 Conclusion Colours are extremely important in pharmaceutical use. There are many controls and limitations on their use. Control of batch to batch colour variation is vital.